Sepsis is a common condition associated with significant morbidity and mortality. Emergency physicians play a key role in the diagnosis and management of this condition.

This paper evaluates key evidence-based updates concerning the management of sepsis and septic shock for the emergency clinician.

Sepsis is a life-threatening syndrome, and rapid diagnosis and management are essential. Antimicrobials should be administered as soon as possible, as delays are associated with increased mortality. Resuscitation targets include mean arterial pressure ≥ 65 mmHg, mental status, capillary refill time, lactate, and urine output. Intravenous fluid resuscitation plays an integral role in those who are fluid responsive. Balanced crystalloids and normal saline are both reasonable options for resuscitation. Early vasopressors should be initiated in those who are not fluid-responsive. Norepinephrine is the recommended first-line vasopressor, and if hypotension persists, vasopressin should be considered, followed by epinephrine. Administration of vasopressors through a peripheral 20-gauge or larger intravenous line is safe and effective. Steroids such as hydrocortisone and fludrocortisone should be considered in those with refractory septic shock.

An understanding of the recent updates in the literature concerning sepsis and septic shock can assist emergency clinicians and improve the care of these patients.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality.

A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality.

A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, -4 << 4 h had more survivors (229/304, 75.3%) than ≤-4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When -4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤-4 h had an odds ratio of 1.96 (1.07-3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94-2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than -4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation.

The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.

Despite recent advances and global improvements in sepsis recognition and supportive care, mortality rates remain high, and adherence to sepsis bundle components in Korea is low. To address this, the Korean Sepsis Alliance, affiliated with the Korean Society of Critical Care Medicine, developed the first sepsis treatment guidelines for Korea based on a comprehensive systematic review and meta-analysis.

A de novo method was used to develop the guidelines. Methodologies included determining key questions, conducting a literature search and selection, assessing the risk of bias, synthesizing evidence, and developing recommendations. The certainty of evidence and the strength of recommendations were determined using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Draft recommendations underwent internal and external review processes and public hearings. The development of these guidelines was supported by a research grant from the Korean Disease Control and Prevention Agency.

In these guidelines, we focused on early treatments for adult patients with sepsis and septic shock. Through the guideline development process, 12 key questions and their respective recommendations were formulated. These include lactate measurement, fluid therapies, target blood pressure, antibiotic administration, use of vasopressors and dobutamine, extracorporeal membrane oxygenation, and echocardiography.

These guidelines aim to support medical professionals in making appropriate decisions about treating adult sepsis and septic shock. We hope these guidelines will increase awareness of sepsis and reduce its mortality rate.

Sepsis is a major cause of mortality worldwide and is the third-leading cause of death in the United States. Sepsis is resource-intensive and requires prompt recognition and treatment to reduce mortality. The impact of sepsis is not only on in-hospital survival but extends into post-discharge quality of life and risk of re-admission. As the understanding of sepsis physiology evolved, so have the recommended screening tools and treatment protocol which challenge prior standards of care. There have been noteworthy efforts by the Surviving Sepsis Campaign, the Third International Consensus Definitions for Sepsis and the Centers for Medicare and Medicaid Services to establish core measure bundles. This review highlights both the 2021 SSC International Guidelines and the 2015 CMS Severe Sepsis/Septic Shock Core Measure Bundle, or SEP-1. Notably, the SEP-1 bundle was implemented as a value-based purchasing program, linking care of sepsis patients to financial incentives. The objective is to explore the most current evidence-based data to inform clinical practice while utilizing the available guidelines as a roadmap.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

It remains poorly understood why only some hemodynamically unstable patients who receive aggressive treatment with vasopressor medications develop limb necrosis.

To determine the incidence of limb necrosis and the factors associated with it following high-dose vasopressor therapy.

A retrospective case-control medical records review was performed of patients aged 18 to 89 years who received vasopressor therapy between 2012 and 2021 in a single academic medical center. The study population was stratified by the development of limb necrosis following vasopressor use. Patients who experienced necrosis were compared with age- and sex-matched controls who did not experience necrosis. Demographic information, comorbidities, and medication details were recorded.

The incidence of limb necrosis following vasopressor administration was 0.25%. Neither baseline demographics nor medical comorbidities differed significantly between groups. Necrosis was present in the same limb as the arterial catheter most often for femoral catheters. The vasopressor dose administered was significantly higher in the necrosis group than in the control group for ephedrine (P = .02) but not for the other agents. The duration of therapy was significantly longer in the necrosis group than in the control group for norepinephrine (P = .001), epinephrine (P = .04), and ephedrine (P = .01). The duration of vasopressin administration did not differ significantly between groups.

The findings of this study suggest that medication-specific factors, rather than patient and disease characteristics, should guide clinical management of necrosis in the setting of vasopressor administration.

In critical care, monitoring adequate tissue oxygenation is essential. Mixed venous oxygen saturation has traditionally been considered the gold standard for measuring cardiac output, which represents systemic oxygen delivery. Studies have shown that hepatic vein saturation is correlated with mixed venous oxygen saturation and mortality. The primary aim of this study was to determine the correlation between hepatic vein saturation and mixed venous saturation, and the impact of clinical characteristics on this correlation.

A systematic review of the literature was performed to identify manuscripts. They must have included patients who received simultaneous mixed venous saturations and hepatic vein saturations, and the data for both must have been explicitly shared. Data were pooled from these studies to analyze the correlation between mixed venous saturation and the corresponding hepatic vein saturation.

A total of 13 studies with 333 patients were included in the final analyses. The average age across these studies was 60.3±5.2. The pooled correlation between the mixed venous saturation and hepatic vein saturation was 0.88, demonstrating a strong correlation between the two. The average mixed venous saturation was 73.3±5.0 while the average hepatic vein saturation was 59.5±11.1.

In these pooled analyses, hepatic vein saturation has a strong correlation with mixed venous saturation. This correlation is not significantly impacted by patient age, weight, or clinical setting. Nonetheless, further prospective studies are needed for confirmation.

Traditionally, the workflow surrounding a general surgery patient allows for a period of evaluation and optimization of underlying medical issues to allow for risk modification; however, in the emergency, this optimization period is largely condensed because of its time-dependent nature. Because the lack of optimization can lead to complications, the ability to rapidly resuscitate the patient, proceed to procedural intervention to control the situation, and manage common medical comorbidities is paramount. This article provides an overview on these subjects.

Shock of any cause leads to end-organ damage due to ischaemia, especially in perfusion-sensitive organs such as the liver. In septic shock, hypoxic hepatitis (S-HH) is defined as the 20-fold increase of the upper normal limit of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) and is associated with a mortality of up to 60%. However, as pathophysiology, dynamics, and treatment differ between septic and cardiogenic shock (CS), the S-HH definition may not be suitable for CS. Therefore, we aim to evaluate if the S-HH definition is applicable in CS patients.

This analysis was based on a registry of all-comer CS patients treated between 2009 and 2019 at a tertiary care centre with exclusion of minors and patients without all necessary ASAT and ALAT values. N = 698. During in-hospital follow-up, 386 (55.3%) patients died. The S-HH was not significantly associated with in-hospital mortality in CS patients. To define HH among patients with CS (C-HH), optimal cut-off values were found to be ≥1.34-fold increase for ASAT and ≥1.51-fold increase for ALAT in serial measurements. The incidence of C-HH was 254/698 patients (36%) and C-HH showed a strong association with in-hospital mortality (odds ratio 2.36, 95% confidence interval: 1.61, 3.49).

The C-HH is a frequent and relevant comorbidity in patients with CS, although its definition varies from the established definition of HH in patients with septic shock. As C-HH contributed to excess mortality risk, these findings emphasize the need for further investigation of therapies reducing the occurrence of C-HH and also improving the associated outcome.

Sepsis is a clinical syndrome encompassing physiologic and biological abnormalities caused by a dysregulated host response to infection. Sepsis progression into septic shock is associated with a dramatic increase in mortality, hence the importance of early identification and treatment. Over the last two decades, the definition of sepsis has evolved to improve early sepsis recognition and screening, standardize the terms used to describe sepsis and highlight its association with organ dysfunction and higher mortality. The early 2000s witnessed the birth of early goal-directed therapy (EGDT), which showed a dramatic reduction in mortality leading to its wide adoption, and the surviving sepsis campaign (SSC), which has been instrumental in developing and updating sepsis guidelines over the last 20 years. Outside of early fluid resuscitation and antibiotic therapy, sepsis management has transitioned to a less aggressive approach over the last few years, shying away from routine mixed venous oxygen saturation and central venous pressure monitoring and excessive fluids resuscitation, inotropes use, and red blood cell transfusions. Peripheral vasopressor use was deemed safe and is rising, and resuscitation with balanced crystalloids and a restrictive fluid strategy was explored. This review will address some of sepsis management's most important yet controversial components and summarize the available evidence from the last two decades.

To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock.

Animal experimental study.

University translational research laboratory.

Fifteen Landrace pigs.

Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.

Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively).

In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.

Vasopressors are widely used in the management of shock among critically ill patients. The physiology of vasopressors and adrenoreceptors and their effects on end organs therefore represent important, high-yield topics for learners in the critical care environment. In this report, we describe our approach to teaching this core concept using the stereotypical human physiologic response when running from a bear, in the context of the relevant supporting literature. We use escaping from a threatening predator as a lens to describe the end-organ effects of activating adrenoreceptors together with the effects of endogenous and exogenous catecholamines and vasopressors. After reviewing this foundational physiology, we transition to the clinical environment, reviewing the pathophysiology of various shock states. We then consolidate our teaching by integrating the physiology of adrenoreceptors with the pathophysiology of shock to understand the appropriateness of each therapy to various shock phenotypes. We emphasize to learners the importance of generating a hypothesis about a patient's physiology, testing that hypothesis with an intervention, and then revising the hypothesis as needed, a critical component in the management of critically ill patients.

Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.

Early initiation of a multimodal treatment strategy in the management of vasopressors during septic shock has been advocated to reduce delays in restoring adequate organ perfusion and to mitigate side effects associated with the administration of high-dose catecholamines. We provide a review that summarises the pathophysiology of vasodilation, the physiologic response to the vascular response, and the different drugs used in this situation, focusing on the need to combine early different vasopressors. Fluid loading being insufficient for counteracting vasoplegia, norepinephrine is usually the first-line vasopressor used to restore hemodynamics. Norepinephrine sparing is discussed in further detail through the concomitant use of adrenergic, vasopressinergic, and renin-angiotensin systems and the optimisation of endothelial reactivity with methylene blue. A blueprint for the construction of new studies is outlined to address the question of vasopressor selection and timing in septic shock.

Non-occlusive mesenteric ischemia (NOMI) is a type of acute mesenteric ischemia (AMI) with a high mortality rate mainly because of a delayed or misdiagnosis. Intra-abdominal sepsis is one of the risk factors for developing NOMI, and its presence makes early diagnosis much more difficult. An increase in routine abdominal surgeries carries a corresponding risk of abdominal infection, which is a complication that should not be overlooked. It is critical that physicians are aware of the possibility for intestinal necrosis in abdominal sepsis patients due to the poor survival rate of NOMI. This review aims to summarize advances in the diagnosis of NOMI, and focuses on the diagnostic challenges of mesenteric ischemia in patients with intra-abdominal sepsis.

Revised guidelines for the management of cardiac arrest have placed greater emphasis on early defibrillation and closed chest compressions; subsequently there has been a significant rise in the number of patients gaining a return of spontaneous circulation (ROSC). As a consequence, emergency medical services have realised the importance of therapies delivered during this phase of care. In some Trusts this includes the use of inotropic agents to augment the cardiovascular system and maintain adequate cerebral and coronary perfusion pressures to mitigate the effects of post-cardiac arrest syndrome. Currently, limited evidence exists with regards to the efficacy of such treatments in the pre-hospital phase.

Retrospective observational analysis of out-of-hospital cardiac arrest patients who received an adrenaline infusion by critical care paramedics. Infusion rates, time of call (ToC) to ROSC and 30-day mortality were compared.

Over a 2-year period, 202 patients were recorded as having an adrenaline infusion commenced. Of these, 25 were excluded as they did not meet criteria or had incomplete data and 22 were excluded as the infusion was stopped at scene; 155 patients were admitted to hospital. There were no survivors in the non-shockable group and three survivors in the shockable group at 30 days. A rare events analysis found no relationship between infusion rate, ToC to ROSC and 30-day mortality (Wald chi2, 1.37).

Commencement of adrenaline infusions in post-ROSC was associated with significant 30-day mortality, especially in non-shockable rhythms. Further research is needed to elucidate whether this intervention has any benefit in the post-ROSC patient.

Acute mesenteric ischemia (AMI) is a group of diseases characterized by an interruption of the blood supply to varying portions of the intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process may progress to life-threatening intestinal necrosis. The incidence is low, estimated at 0.09-0.2% of all acute surgical admissions, but increases with age. Although the entity is an uncommon cause of abdominal pain, diligence is required because if untreated, mortality remains in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques is evolving and provides new treatment options. Lastly, a focused multidisciplinary approach based on early diagnosis and individualized treatment is essential. Thus, we believe that updated guidelines from World Society of Emergency Surgery are warranted, in order to provide the most recent and practical recommendations for diagnosis and treatment of AMI.

Oxygen is needed to generate aerobic adenosine triphosphate and energy that is required to support vital cellular functions. Oxygen delivery (DO2) to the tissues is determined by convective and diffusive processes. The ability of the body to adjust oxygen extraction (ERO2) in response to changes in DO2 is crucial to maintain constant tissue oxygen consumption (VO2). The capability to increase ERO2 is the result of the regulation of the circulation and the effects of the simultaneous activation of both central and local factors. The endothelium plays a crucial role in matching tissue oxygen supply to demand in situations of acute drop in tissue oxygenation. Tissue oxygenation is adequate when tissue oxygen demand is met. When DO2 is severely compromised, a critical DO2 value is reached below which VO2 falls and becomes dependent on DO2, resulting in tissue hypoxia. The different mechanisms of tissue hypoxia are circulatory, anaemic, and hypoxic, characterised by a diminished DO2 but preserved capacity of increasing ERO2. Cytopathic hypoxia is another mechanism of tissue hypoxia that is due to impairment in mitochondrial respiration that can be observed in septic conditions with normal overall DO2. Sepsis induces microcirculatory alterations with decreased functional capillary density, increased number of stopped-flow capillaries, and marked heterogeneity between the areas with large intercapillary distance, resulting in impairment of the tissue to extract oxygen and to satisfy the increased tissue oxygen demand, leading to the development of tissue hypoxia. Different therapeutic approaches exist to increase DO2 and improve microcirculation, such as fluid therapy, transfusion, vasopressors, inotropes, and vasodilators. However, the effects of these agents on microcirculation are quite variable.

Vasopressors are the cornerstone of hemodynamic management in patients with septic shock. Norepinephrine is currently recommended as the first-line vasopressor in these patients. In addition to norepinephrine, there are many other potent vasopressors with specific properties and/or advantages that act on vessels through different pathways after activation of specific receptors; these could be of interest in patients with septic shock. Dopamine is no longer recommended in patients with septic shock because its use is associated with a higher rate of cardiac arrhythmias without any benefit in terms of mortality or organ dysfunction. Epinephrine is currently considered as a second-line vasopressor therapy, because of the higher rate of associated metabolic and cardiac adverse effects compared with norepinephrine; however, it may be considered in settings where norepinephrine is unavailable or in patients with refractory septic shock and myocardial dysfunction. Owing to its potential effects on mortality and renal function and its norepinephrine-sparing effect, vasopressin is recommended as second-line vasopressor therapy instead of norepinephrine dose escalation in patients with septic shock and persistent arterial hypotension. However, two synthetic analogs of vasopressin, namely, terlipressin and selepressin, have not yet been employed in the management of patients with septic shock, as their use is associated with a higher rate of digital ischemia. Finally, angiotensin Ⅱ also appears to be a promising vasopressor in patients with septic shock, especially in the most severe cases and/or in patients with acute kidney injury requiring renal replacement therapy. Nevertheless, due to limited evidence and concerns regarding safety (which remains unclear because of potential adverse effects related to its marked vasopressor activity), angiotensin Ⅱ is currently not recommended in patients with septic shock. Further studies are needed to better define the role of these vasopressors in the management of these patients.

Vasodilatory shock, such as septic shock, requires personalized management which include adequate fluid therapy and vasopressor treatments. While these potent drugs are numerous, they all aim to counterbalance the vasodilatory effects of a systemic inflammatory response syndrome. Their specific receptors include α- and β-adrenergic receptors, arginine-vasopressin receptors, angiotensin II receptors and dopamine receptors. Consequently, these may be associated with severe adverse effects, including acute mesenteric ischemia (AMI). As the risk of AMI depends on drug class, we aimed to review the evidence of plausible associations by performing a worldwide pharmacovigilance analysis based on the World Health Organization database, VigiBase®. Among 24 million reports, 104 AMI events were reported, and disproportionality analyses yielded significant association with all vasopressors, to the exception of selepressin. Furthermore, in a comprehensive literature review, we detailed mechanistic phenomena which may enhance vasopressor selection, in the course of treating vasodilatory shock.

Patients undergoing heart transplant (HT) and ventricular assist device (VAD) implant may experience intra- and postoperative complications requiring high-dose vasopressor agents and/or mechanical circulatory support. These complications increase the risk of nonocclusive bowel ischemia (NOBI) and inadequate enteral nutrition (EN) delivery, and guidance for this high-risk patient population is limited. To optimize nutrition support practices in this patient population at our institution, we created the High-Risk Nutrition Support Protocol (HRNSP) to improve nutrient delivery and promote safer EN practices in the setting of NOBI risk factors after HT and VAD implant.

We developed and implemented a nutrition support protocol as a quality improvement (QI) initiative. Data were obtained before (n = 62) and after (n = 52) protocol initiation. We compared nutrition and clinical outcomes between the pre- and post-intervention groups.

Fewer calorie deficits (P < 0.001), fewer protein deficits (P < 0.001), a greater proportion of calorie/protein needs met (P < 0.001), zero NOBI cases (0%), and decreased intensive care unit (ICU) length of stay (LOS) (P = 0.005) were observed with 100% (n = 52 of 54) HRNSP implementation success. Increased use of parenteral nutrition did not increase central line-associated bloodstream infections (P = 0.46). There was no difference in hospital LOS (P = 0.44) or 90-day and 1-year mortality (P = 0.56, P = 0.35).

This single-center, QI pre- and post-protocol intervention outcome study suggests that implementing and adhering to a nutrition support protocol for VAD implant/HT patients with hemodynamic complications increases nutrient delivery and is associated with reduced ICU LOS and NOBI.

The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model.

Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3+ counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10.

Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3+ mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE (p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver (p ˂ 0.01).

Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.

Cardiovascular disturbances are a frequent occurrence in neonatal sepsis. Preterm and term infants are particularly vulnerable due to the unique features of their cardiovascular function and reserve, compared to older children and adults. The clinical manifestations of neonatal sepsis are a product of the variable inflammatory pathways involved (warm vs. cold shock physiology), developmental state of the cardiovascular system, and hormonal responses. Targeted neonatal echocardiography has played an important role in advancing our knowledge, may help delineate specific hemodynamic phenotypes in real-time, and supports an individualized physiology-based management of sepsis-associated cardiovascular dysfunction. IMPACT: Cardiovascular dysfunction is a common sequela of sepsis. This review aims to highlight the pathophysiological mechanisms involved in hemodynamic disturbance in neonatal sepsis, provide insights from targeted neonatal echocardiography-based clinical studies, and suggest its potential incorporation in day-to-day management.

Catecholamines are recommended as first-line drugs to treat hemodynamic instability after out-of-hospital cardiac arrest (OHCA). The benefit-to-risk ratio of catecholamines is dose dependent, however, their effect on metabolism and organ function early after OHCA has not been investigated.

The Post-Cardiac Arrest Syndrome (PCAS) pilot study was a prospective, observational, multicenter study. The primary outcomes of this analysis were association between norepinephrine/cumulative catecholamines doses and neuron specific enolase (NSE)/lactate concentration over the first 72 hours after resuscitation. The association was adjusted for proven OHCA mortality predictors and verified with propensity score matching (PSM).

Overall 148 consecutive OHCA patients; aged 18-91 (62.9 ± 15.27), 41 (27.7%) being female, were included. Increasing norepinephrine and cumulative catecholamines doses were significantly associated with higher NSE concentration on admission (r = 0.477, p < 0.001; r = 0.418, p < 0.001) and at 24 hours after OHCA (r = 0.339, p < 0.01; r = 0.441, p < 0.001) as well as with higher lactate concentration on admission (r = 0.404, p < 0.001; r = 0.280, p < 0.01), at 24 hours (r = 0.476, p < 0.00; r = 0.487, p < 0.001) and 48 hours (r = 0.433, p < 0.01; r = 0.318, p = 0.01) after OHCA. The associations remained significant up to 48 hours in non-survivors after PSM.

Increasing the dose of catecholamines is associated with higher lactate and NSE concentration, which may suggest their importance for tissue oxygen delivery, anaerobic metabolism, and organ function early after OHCA.

Limited information is currently available on the impact of vasoactive medications in intensive care (ICU) and long-term outcomes. The main objective of our study was to describe the association between the use of inotropes and/or vasopressors and ICU mortality. Secondary objectives were to evaluate the association between the use of vasoactive drugs and in-hospital as well as 1-year all-cause mortality in ICU survivors.

FROG-ICU was a prospective, observational, multi-centre cohort designed to investigate long-term mortality of critically ill adult patients. Cox proportional hazards models were used to evaluate the association between the use of inotropes and/or vasopressors and ICU mortality, as well as in-hospital and 1-year all-cause mortality in a propensity-score matched cohort.

The study included 2087 patients, 939 of whom received inotropes and/or vasopressors during the initial ICU stay. Patients treated with vasoactive medications were older and had a more severe clinical presentation. In a propensity score-matched cohort of 1201 patients, ICU mortality was higher in patients who received vasoactive medications (HR of 1.40 [1.10 - 1.78], p = 0.007). One thousand six hundred thirty-five patients survived the index ICU hospitalisation. There was no significant difference according to the use of inotropes and/or vasopressors in the propensity-score matched cohort on in-hospital mortality (HR of 0.94 [0.60 - 1.49], p = 0.808) as well as one-year all-cause mortality (HR 0.94 [0.71 - 1.24], p = 0.643).

Inotropic and/or vasopressor therapy is a strong predictor of in-ICU death. However, the use of inotropes and/or vasopressors during ICU admission was not associated with a worse prognosis after ICU discharge.